Now showing items 21-31 of 31

    • Screening the Human Genome for New Mitochondrial and Longevity Regulators 

      Ling, Alvin Jee Yee (2015-05-18)
      Over the past two decades, genes and pathways have been discovered that can prolong lifespan and delay the onset of age-related diseases. The vast majority of these longevity genes were discovered in screens conducted in ...
    • Selective Sirt2 inhibition by ligand-induced rearrangement of the active site 

      Rumpf, Tobias; Schiedel, Matthias; Karaman, Berin; Roessler, Claudia; North, Brian J.; Lehotzky, Attila; Oláh, Judit; Ladwein, Kathrin I.; Schmidtkunz, Karin; Gajer, Markus; Pannek, Martin; Steegborn, Clemens; Sinclair, David A.; Gerhardt, Stefan; Ovádi, Judit; Schutkowski, Mike; Sippl, Wolfgang; Einsle, Oliver; Jung, Manfred (Nature Pub. Group, 2015)
      Sirtuins are a highly conserved class of NAD+-dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 ...
    • The Sirt1 activator SRT3025 provides atheroprotection in Apoe−/− mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression 

      Miranda, Melroy X.; van Tits, Lambertus J.; Lohmann, Christine; Arsiwala, Tasneem; Winnik, Stephan; Tailleux, Anne; Stein, Sokrates; Gomes, Ana P.; Suri, Vipin; Ellis, James L.; Lutz, Thomas A.; Hottiger, Michael O.; Sinclair, David A.; Auwerx, Johan; Schoonjans, Kristina; Staels, Bart; Lüscher, Thomas F.; Matter, Christian M. (Oxford University Press, 2014)
      Aims The deacetylase sirtuin 1 (Sirt1) exerts beneficial effects on lipid metabolism, but its roles in plasma LDL-cholesterol regulation and atherosclerosis are controversial. Thus, we applied the pharmacological Sirt1 ...
    • The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth 

      Firestein, Ron; Blander, Gil; Michan, Shaday; Oberdoerffer, Philipp; Luikenhuis, Sandra; de Cabo, Rafael; Guarente, Leonard P.; Ogino, Shuji; Campbell, Jennifer; Bhimavarapu, Anupama; Fuchs, Charles Stewart; Hahn, William C.; Sinclair, David Andrew (Public Library of Science, 2008)
      Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same ...
    • SIRT1 Is Required for AMPK Activation and the Beneficial Effects of Resveratrol on Mitochondrial Function 

      Price, N; Gomes, Ana P.; Ling, Alvin Jee Yee; Duarte, Filipe V.; Martin-Montalvo, Alejandro; North, Brian; Agarwal, Beamon; Ye, Lan; Ramadori, Giorgio; Teodoro, Joao S.; Hubbard, B; Varela, Ana T.; Davis, James G.; Varamini, Behzad; Hafner, Angela; Moaddel, Ruin; Rolo, Anabela P.; Coppari, Roberto; Palmeira, Carlos M.; de Cabo, Rafael; Baur, Joseph A.; Sinclair, David Andrew (Elsevier BV, 2012)
      Resveratrol induces mitochondrial biogenesis and protects against metabolic decline, but whether SIRT1 mediates these benefits is the subject of debate. To circumvent the developmental defects of germline SIRT1 knockouts, ...
    • SIRT1 mRNA Expression May Be Associated With Energy Expenditure and Insulin Sensitivity 

      Rutanen, Jarno; Yaluri, Nagendra; Modi, Shalem; Itkonen, Paula; Kainulainen, Sakari; Yamamoto, Hiroyasu; Lagouge, Marie; Elliott, Peter; Westphal, Christoph; Auwerx, Johan; Laakso, Markku; Sinclair, David Andrew; Vänttinen, Markku; Pihlajamäki, Jussi (American Diabetes Association, 2010)
      Objective: Sirtuin 1 (SIRT1) is implicated in the regulation of mitochondrial function, energy metabolism, and insulin sensitivity in rodents. No studies are available in humans to demonstrate that SIRT1 expression in ...
    • Sirtuin1 Over-Expression Does Not Impact Retinal Vascular and Neuronal Degeneration in a Mouse Model of Oxygen-Induced Retinopathy 

      Michan, Shaday; Juan, Aimee M.; Hurst, Christian G.; Cui, Zhenghao; Evans, Lucy P.; Hatton, Colman J.; Pei, Dorothy T.; Ju, Meihua; Sinclair, David A.; Smith, Lois E. H.; Chen, Jing (Public Library of Science, 2014)
      Proliferative retinopathy is a leading cause of blindness, including retinopathy of prematurity (ROP) in children and diabetic retinopathy in adults. Retinopathy is characterized by an initial phase of vessel loss, leading ...
    • Small-Molecule Allosteric Activators of Sirtuins 

      Sinclair, David Andrew; Guarente, Leonard (Annual Reviews, 2014)
      The mammalian sirtuins (SIRT1-7) are NAD(+)-dependent lysine deacylases that play central roles in cell survival, inflammation, energy metabolism, and aging. Members of this family of enzymes are considered promising ...
    • SRT1720 improves survival and healthspan of obese mice 

      Minor, Robin K.; Baur, Joseph A.; Gomes, Ana P.; Ward, Theresa M.; Csiszar, Anna; Mercken, Evi M.; Abdelmohsen, Kotb; Shin, Yu-Kyong; Canto, Carles; Scheibye-Knudsen, Morten; Krawczyk, Melissa; Irusta, Pablo M.; Martín-Montalvo, Alejandro; Hubbard, Basil; Zhang, Yongqing; Lehrmann, Elin; White, Alexa A.; Price, Nathan; Swindell, William; Pearson, Kevin J.; Becker, Kevin G.; Bohr, Vilhelm A.; Gorospe, Myriam; Egan, Josephine M.; Talan, Mark I.; Auwerx, Johan; Westphal, Christoph H.; Ellis, James L.; Ungvari, Zoltan; Vlasuk, George P.; Elliott, Peter J.; Sinclair, David Andrew; de Cabo, Rafael (Nature Publishing Group, 2011)
      Sirt1 is an NAD1-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was ...
    • SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass 

      Mercken, Evi M; Mitchell, Sarah J; Martin-Montalvo, Alejandro; Minor, Robin K; Almeida, Maria; Gomes, Ana P; Scheibye-Knudsen, Morten; Palacios, Hector H; Licata, Jordan J; Zhang, Yongqing; Becker, Kevin G; Khraiwesh, Husam; González-Reyes, José A; Villalba, José M; Baur, Joseph A; Elliott, Peter; Westphal, Christoph; Vlasuk, George P; Ellis, James L; Sinclair, David A; Bernier, Michel; de Cabo, Rafael (BlackWell Publishing Ltd, 2014)
      Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean ...
    • Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age‐related insulin resistance 

      Mohamad, Mashani; Mitchell, Sarah Jayne; Wu, Lindsay Edward; White, Melanie Yvonne; Cordwell, Stuart James; Mach, John; Solon‐Biet, Samantha Marie; Boyer, Dawn; Nines, Dawn; Das, Abhirup; Catherine Li, Shi‐Yun; Warren, Alessandra; Hilmer, Sarah Nicole; Fraser, Robin; Sinclair, David Andrew; Simpson, Stephen James; de Cabo, Rafael; Le Couteur, David George; Cogger, Victoria Carroll (John Wiley and Sons Inc., 2016)
      Summary While age‐related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole‐body insulin handling and its role in age‐related ...